Snips will help prevent a graft-versus-host reaction
Transplantation of hematopoietic cells isolated from bone marrow or other sources is used to treat a wide range of hematological diseases, such as leukemia. One of the most serious side effects of hematopoietic cell transplantation and a common cause of death of patients undergoing this procedure is the "graft versus host" reaction (GVHD). This reaction develops after the donor's immune cells begin to circulate in the patient's circulatory system and recognize his "new host" tissues as foreign. In such cases, the immune system of the transplant begins to destroy the patient's tissues, usually his liver, gastrointestinal tract or skin.
The risk of developing GVHD, especially its acute form, is significantly reduced when transplanting material from related donors compatible in the HLA system (human leukocyte antigens, human leukocyte antigens), traditionally used to determine the compatibility of the donor and recipient. At the same time, when transplanting even fully compatible hematopoietic cells from unrelated donors, almost all patients develop severe forms of acute GVHD.
Researchers at the Fred Hutchinson Cancer Research Center (Seattle, Washington) have found an explanation for this phenomenon. They conducted a retrospective analysis, in which the DNA of 4205 patients who underwent hematopoietic cell transplantation in different medical institutions in the United States was analyzed for the content of 1120 single-nucleotide polymorphisms (SNPs, from the English single-nucleotide polymorphisms, SNP) located on chromosome 6. On this chromosome are the genes of the so-called major histocompatibility complex (major histocompatibility complex, MHC), including coding HLA antigens.
As a result, two snips were identified, which are markers of the development of acute GVHD or its absence. These snips are part of the main histocompatibility complex (MHC), but have nothing in common with the genes encoding HLA antigens.
The results of the study showed that the mismatch of identified snips in the donor and recipient is associated with an increased risk of acute GVHD and death of the patient. The authors suggest that the reason for this lies in the genes localized in the immediate vicinity of these snips.
Despite the importance of this finding, it can only help patients who have several potential compatible unrelated donors at once. Unfortunately, in reality, many patients are deprived of such a choice.
In the future, scientists plan to sequence the DNA regions adjacent to the identified snips in order to identify the genes directly responsible for patient survival and the risk of developing acute GVHD.
Article by Effie W. Petersdorf et al. MHC-Resident Variation Affects Risks After Unrelated Donor Hematopoietic Cell Transplantation is published in the journal Science Translational Medicine.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Fred Hutchinson Cancer Research Center:
Researchers uncover new genetic clues to why most bone marrow transplant patients develop graft-versus-host disease.17.09.2012